According to the lipid hypothesis, abnormally high cholesterol levels (hypercholesterolemia), or, more correctly, higher concentrations of LDL and lower concentrations functional HDL are strongly associated with heart disease because these promote atheroma development in arteries (atherosclerosis). In contrast, HDL particles (especially large HDL) have been identified as a mechanism by which cholesterol and inflammatory mediators can be removed from atheroma.

Increased concentrations of HDL correlate with lower rates of atheroma progressions and even regression. The relation of cholesterol to CHD, termed the "lipid hypothesis," is still hotly debated.

Atherosclerosis leads to myocardial infarction (heart attacks), stroke and peripheral vascular disease. Since higher blood concentrations of LDL, especially the smaller and denser LDL particles, contribute to this process, they are often termed "bad cholesterol" because they have been linked to atheroma formation, while high concentrations of functional HDL, which can remove cholesterol from cells and atheroma, offer protection. These balances are mostly genetically determined but can be changed by body build, medications, food choices and other factors.

Cholesterol Testing

Most testing methods for LDL do not actually measure LDL in their blood, much less particle size. For cost reasons, LDL values have long been estimated using the Friedewald formula: [total cholesterol] − [total HDL] − 20% of the triglyceride value = estimated LDL. The basis of this is that Total cholesterol is defined as the sum of HDL, LDL, and VLDL. Ordinarily just the total, HDL, and triglycerides are actually measured. The VLDL is estimated as one-fifth of the triglycerides. It is important to fast for at least 8-12 hours before the blood test because the triglyceride level varies significantly with food intake.

A blood sample taken after fasting is taken by a doctor or a home cholesterol monitoring device to determine a lipoprotein profile. This measures total cholesterol, LDL (bad) cholesterol, HDL (good) cholesterol and triglycerides. It is recommended to have cholesterol tested more frequently than 5 years if a person: has total cholesterol of 200 mg/dL or more, is a man over age 45 or a woman over age 50, has HDL (good) cholesterol less than 40 mg/dL, or other risk factors for heart disease and stroke.

It is recommended by the American Heart Association to test cholesterol every 5 years for people aged 20 years or older

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